The pineal gland (also called the pineal body, epiphysis cerebri, epiphysis or the "third eye") is a small endocrine gland in the vertebrate brain. It produces melatonin, a hormone that affects the modulation of wake/sleep patterns and photoperiodic (seasonal) functions.[1][2] It is shaped like a tiny pine cone (hence its name), and is located near to the center of the brain, between the two hemispheres, tucked in a groove where the two rounded thalamic bodies join. Unlike much of the rest of the brain, the pineal gland is not isolated from the body by the blood-brain barrier system.[3]

In some vertebrates, exposure of the pineal to light can directly set off a chain reaction of enzymatic events which regulate circadian rhythms.[8] Some early vertebrate fossil skulls have a pineal foramen (opening). This corroborates with the physiology of the modern "living fossils", the lamprey and the tuatara, and some other vertebrates which have a parietal organ or "third eye" which, in some of them, is photosensitive. The third eye represents evolution’s earlier approach to photoreception.[9] The structures of the third eye in the tuatara are homologous to the cornea, lens and retina, though the latter resembles that of an octopus rather than a vertebrate retina. The asymmetrical whole consists of the "eye" to the left and the pineal sac to the right. "In animals that have lost the parietal eye, including mammals, the pineal sac is retained and condensed into the form of the pineal gland."[9]

Fossils seldom preserve soft anatomy. The brain of the Russian Melovatka bird, about 90 million years old, is an exception, and it shows a larger-than-expected parietal eye and pineal gland.[10]

The pineal gland was originally believed to be a "vestigial remnant" of a larger organ (much as the appendix was thought to be a vestigial digestive organ). Aaron Lerner and colleagues at Yale University discovered that melatonin, the most potent compound then known to lighten frog skin, was present in the highest concentrations in the pineal.[11]Melatonin is a derivative of the amino acidtryptophan, which also has other functions in the central nervous system. The production of melatonin by the pineal gland is stimulated by darkness and inhibited by light.[12] Photosensitive cells in the retina detect light and directly signal the suprachiasmatic nucleus (SCN), entraining it to the 24 hour clock. Fibers project from the SCN to the paraventricular nuclei (PVN), which relay the circadian signals to the spinal cord and out via the sympathetic system to superior cervical ganglia (SCG), and from there into the pineal gland. The function(s) of melatonin in humans is not clear; it is commonly prescribed for the treatment of circadian rhythm sleep disorders.

There is complementary evidence that the pineal gland is involved in the regulation of sleep in humans and of the full circadian rhythm in other species. It is interesting to note that in some species such as lizards the gland contains light sensitive neurons.

The compound pinoline is also produced in the pineal gland; it is one of the beta-carbolines. The biological activity of this molecule is of interest as a potential free radical scavenger (antioxidant), similar to that function of melatonin.[22] It also acts as an endogenous MAOI.

The secretory activity of the pineal gland has only relatively recently become understood. Historically, its location close to the geographical centre in the brain suggested to philosophers that it possessed particular importance. This combination led to its being a "mystery" gland with myth, superstition and metaphysical theories surrounding its perceived function.

Galen was of the opinion that it might be responsible for the flow of thought. [23]

René Descartes, who dedicated much time to the study of the pineal gland,[24] called it the "seat of the soul".[25] He believed that it was the point of connection between the rational soul or intellect and the body.[26]

The notion of a 'pineal-eye' is central to the philosophy of the seminal French writer Georges Bataille, which is analyzed at length by literary scholar Denis Hollier in his study Against Architecture.[27] In this work Hollier discusses how Bataille uses the concept of a 'pineal-eye' as a reference to a blind-spot in Western rationality.